N-Arachidonyl dopamine sensitizes rat capsaicin-sensitive lung vagal afferents via activation of TRPV1 receptors

We investigated the effect of N-arachidonyl dopamine (NADA), an endogenous agonist of both transient receptor potential vanilloid 1 (TRPV1) and cannabinoid CB1 receptors, on the sensitivity of rat capsaicin-sensitive lung vagal afferent (CSLVA) fibers. In artificially ventilated rats, an intravenous infusion of NADA (400 μg/kg/ml, 0.5 ml/min for 2 min) mildly elevated the baseline CSLVA fiber activity, whereas it markedly potentiated CSLVA fiber responses to a right atrial injection of capsaicin or adenosine, and to lung inflation. The potentiating effect on CSLVA fiber sensitivity to an adenosine injection or lung inflation was blocked by capsazepine pretreatment (a TRPV1 receptor antagonist), but was unaffected by AM251 pretreatment (a CB1 receptor antagonist). In spontaneously breathing rats, a NADA infusion similarly potentiated the CSLVA fiber-mediated apneic response evoked by an adenosine injection, and this potentiating effect was also prevented by capsazepine pretreatment. We concluded that NADA at the dose tested non-specifically increases CSLVA fiber sensitivity to chemical and mechanical stimulation via activation of TRPV1 receptors.